Retroviral v-myc infection of primary fetal liver cells: transformation of monocytes in vitro.

Oncogenes carried by retroviruses can alter the growth properties of many cell types. We examined the molecular mechanism by which a retrovirus containing one or a combination of oncogenes can transform and immortalize hematopoietic cells. Murine fetal liver cells were used as an enriched source of early hematopoietic cell progenitors; the cells were infected with a series of recombinant murine retroviruses capable of expressing the avian v-myc, v-H-ras and v-raf oncogenes. Three factor-independent cell lines were obtained: FL-ras/myc, FL-J2 (v-raf/v-myc) and FL-myc, a unique cell line generated using a single oncogene. Cytochemical, morphologic and phenotypic analyses indicated that these cell lines were of the monocyte lineage. Southern and Northern blot analyses revealed that the three cell lines had integrated viral DNA and were expressing the mRNA transcripts corresponding to these viral oncogenes. To examine the mechanism of factor independence, supernatants from these cell lines were tested for CSF-1 activity. Supernatants from FL-myc and FL-ras/myc cells were shown to contain CSF-1 activity and Northern blot analysis of the three cell lines revealed the presence of mRNA transcripts for the CSF-1 and c-fms genes. It is possible that the growth factor independence of these cell lines is related to the development of autocrine-induced proliferation.